title: Supratentorial primitive neuroectodermal tumors of the central nervous system in adults: molecular and histopathologic analysis of 12 cases.
abstract: Advances in understanding the molecular basis of primitive neuroectodermal tumors of the central nervous system (CNS-PNET) biology are critical to improve patient outcome. Recently, new data on their molecular features have been reported, suggesting that supratentorial PNET (s-PNET) in adult patients may represent a specific tumor entity among CNS-PNETs. In this study, we analyzed the clinicopathologic and molecular features of 12 cases of s-PNET in adult patients. The follow-up analysis showed that these tumors have an aggressive clinical behavior. At the histopathologic level, they resembled their pediatric counterpart, showing a variable spectrum of neuronal differentiation. These cases did not show astrocytic differentiation; therefore, they did not qualify for the differential diagnosis of glioblastoma variants. The tumors were also screened for mutation of TP53, IDH1, IDH2, and β-catenin, using single strand conformation polymorphism-based and sequencing assays, and were analyzed for c-myc/N-myc gene copy numbers with a quantitative polymerase chain reaction-based method. The strand conformation polymorphism-based mutational analysis showed that 5 tumors harbored TP53 mutations. In 2 cases, a mutation at codon 132 of the IDH1 gene was also found. No mutations of the β-catenin or IDH2 genes were identified. No cases presented c-myc or N-myc amplifications. Only 1 case presented overexpression of epidermal growth factor receptor. In conclusion, our data show a high incidence of TP53 mutations in this group of tumors and show, in comparison with pediatric s-PNET, the absence of amplification of the c-myc/N-myc genes, indicating that s-PNET in adult patients may represent a specific subset of tumors among CNS-PNETs.
authors.affiliation: Institute of Neuropathology, University of Bonn Medical Center, Bonn, Germany. mgessimd@yahoo.com
authors.forename: Marco
authors.initials: M
authors.lastname: Gessi
authors.forename: Prashanth
authors.initials: P
authors.lastname: Setty
authors.forename: Michele
authors.initials: M
authors.lastname: Bisceglia
authors.forename: Anja
authors.initials: A
authors.lastname: zur Muehlen
authors.forename: Libero
authors.initials: L
authors.lastname: Lauriola
authors.forename: Andreas
authors.initials: A
authors.lastname: Waha
authors.forename: Felice
authors.initials: F
authors.lastname: Giangaspero
authors.forename: Torsten
authors.initials: T
authors.lastname: Pietsch
mesh_terms: D000328:Adult; D003131:Combined Modality Therapy; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D017809:Fatal Outcome; D005260:Female; D016259:Genes, myc; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000071447:N-Myc Proto-Oncogene Protein; D018242:Neuroectodermal Tumors, Primitive / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D009687:Nuclear Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D015173:Supratentorial Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D004273:DNA, Neoplasm; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human